Inhibitory effect of Sargassum latifolium extract on hypoxia pathway in colon cancer cells


  • Amira M. Gamal- Eldeen Clinical Laboratory Sciences Department, College of Applied Medical Sciences, Taif ‎University, P.O. Box 11099, Taif 21944, Saudi Arabia; High Altitude Research Center, Prince Sultan Medical Complex, Al-Hawiyah, Taif ‎University, Taif, Saudi Arabia
  • Bassem M. Raafat Radiological Sciences Department, College of Applied Medical Sciences, Taif University, ‎P.O. Box 11099, Taif 21944, Saudi Arabia
  • Sherien M. ‎El- Daly Medical Biochemistry Department, Medical Research Division, National Research Centre, ‎‎33 El Buhouth St. Dokki, Cairo, 12622, Egypt‎; Cancer Biology and Genetics Laboratory, Centre of Excellence for Advanced Sciences, ‎National Research Centre, 33 El Buhouth St. Dokki, Cairo, 12622, Egypt
  • Cinderella A. Fahmy Cancer Biology and Genetics Laboratory, Centre of Excellence for Advanced Sciences, ‎National Research Centre, 33 El Buhouth St. Dokki, Cairo, 12622, Egypt; Biochemistry Department, Medical Research Division, National Research Centre, ‎‎33 El Buhouth St. Dokki, Cairo, 12622, Egypt‎
  • Mazen M Almehmadi Clinical Laboratory Sciences Department, College of Applied Medical Sciences, Taif ‎University, P.O. Box 11099, Taif 21944, Saudi Arabia
  • Fayez Althobaiti High Altitude Research Center, Prince Sultan Medical Complex, Al-Hawiyah, Taif ‎University, Taif, Saudi Arabia; Biotechnology Department, Faculty of Science, Taif University, P.O. Box 11099, Taif ‎‎21944, ‎Saudi Arabia



Sargassum latifolium, ‎(Turner) C. Agarth, 1820, is an edible brown alga that was collected from red seashores in Egypt. Colon cancer is a lethal disease world-wide. Hypoxia is a key player in progressive colon tumor growth and stemness. This work was planned to extract water-soluble polysaccharide from S. latifolium, to separate its fractions (SL1, SL2, SL3, and SL4) and hence to investigate their anti-hypoxia characteristics in colon cancer HCT-116 cells. Algal fractions cytotoxicity was assayed by MTT; DNA staining was used to analyze apoptosis and necrosis; total hypoxia status was assessed by pimonidazole, HIF-1α and HIF-1β were estimated by ELISA, and hsa-miRNA-21-5p and hsa-miRNA-210-3p were analyzed by qPCR. The results indicated that SL1 and SL4 are cytotoxic agents against HCT-116 cells through enhancing apoptosis. SL1and SL4 were potent inhibitor of total cell hypoxia (p < 0.001). Both fractions significantly suppressed the expression of miR-21 (p < 0.01) and miR-210 (p < 0.001), and the concentration of HIF-1α protein (p < 0.01 and p < 0.001, respectively), while only SL1 inhibited HIF-1β protein concentration (p < 0.05). Taken together S. latifolium polysaccharide extract fractions SL1 and SL4 exhibited anti-hypoxic property in HCT-116 cells through mechanistic role in the expression of hypoxia regulators miRNA-21 and miRNA-210, and accordingly in HIF-1α and HIF-1β biosynthesis‎.


Download data is not yet available.


Asker, M. S., S.M Mohamed, F. M. Ali and O.H. El-Sayed. 2007. Chemical Structure and Antiviral Activity of Water-soluble Sulfated Polysaccharides from Surgassum dentifolium. J. App. Sci. Res. 3: 1178-1185.
Baskić, D., S. Popović, P. Ristić and N. N. Arsenijević. 2006. Analysis of cycloheximide-‎induced apoptosis in human leukocytes: fluorescence microscopy using annexin ‎V/propidium iodide versus acridine orange/ethidium bromide. Cell Biol. Int. 30: 924-‎‎932.
Birner, P., M. Schindl, A. Obermair, C. Plank, G. Breitenecker and G. Oberhuber. 2000. Overexpression of ‎hypoxia-inducible factor 1alpha is a marker for an unfavorable prognosis in early-stage ‎invasive cervical cancer. Cancer Res. 60: 4693-4696.‎
Burtin, P. 2003. Nutritional value of seaweeds. Electronic J. Environ. Agric. Food Chem. 2: 498-503.
Dar, A., H. S. Baig, S. M. Saifuallah, V. U. Ahmad, N. Yasmeen and M. Nizamuddin. 2007. Effect of ‎seasonal variation on the anti-inflammatory activity of Sargassum wightii growing on the N. ‎Arabian Sea coast of Pakistan. J. Exp. Mar. Boil. Ecol. 351: 1-9. ‎
Dery, M. A., M. D. Michaud and D. E. Richard. 2004. Hypoxia-inducible factor 1: regulation by hypoxic and non-‎hypoxic activators. Int. J. Biochem. Cell Bio. 37: 535-540‎
D'Ignazio, L., D. Shakir, M. Batie, H. A. Muller and S. Rocha. 2020. HIF-1β Positively Regulates ‎NF-κB Activity via Direct Control of TRAF6. Int. J. Mol. Sci. 21:‎‎ 3000.
Ellamie, A. M., W. A. Fouda, W. M. Ibrahim and G. Ramadan. 2020. Dietary supplementation of brown seaweed (Sargassum latifolium) alleviates the environmental heat stress-induced toxicity in male Barki sheep (Ovis aries). J. Therm. Biol. 89: 102561.
Ercin, M. E., Ö. Bozdoğan, T. Çavuşoğlu, N. Bozdoğan, P. Atasoy and M. Koçak. 2019. ‎Hypoxic Gene Signature of Primary and Metastatic Melanoma Cell Lines: Focusing on HIF-1β and ‎NDRG-1. Balkan Med. J. 37: 15-23.
Fasanaro, P., Y. D'Alessandra, V. Di Stefano, R. Melchionna and S. Romani. 2008. ‎MicroRNA-210 modulates endothelial cell response to hypoxia and inhibits the receptor ‎tyrosine kinase ligand Ephrin-A3. J. Biol. Chem. 283: 15878-15883.‎‏
Gamal-Eldeen, A. M., M. A. M. Abo-Zeid and E. F. Ahmed. 2013. Anti-genotoxic effect of the Sargassum ‎dentifolium extracts: Prevention of chromosomal aberrations, micronuclei, and DNA ‎fragmentation.‏‎ Exp. Tox. Path. ‏‎ 65: 27-34.
Gamal-Eldeen, A. M., E. F. Ahmed and M. A. M. Abo-Zeid. 2009. In vitro cancer chemopreventive properties of ‎polysaccharide extract from the brown alga, Sargassum latifolium. Food Chem. ‎Tox. 47: 1378-1384.‎
Hansen, M. B., S. E. Nielsen and K. Berg. 1989. Re-examination and further development of ‎a precise ‎and rapid dye method for measuring cell growth/cell kill. J. Immunol. ‎Methods. 119: 203-210. ‎
Huang, Y., D. Lin and CM. Taniguchi. 2017. Hypoxia inducible factor (HIF) in the tumor microenvironment: ‎friend or foe? Sci. China Life Sci. 60: 1114-24.‎
Jimenez-Escrig, A. and F. Sanchez-Muniz. 2000. Dietary Fiber from edible seaweeds: chemical structure, physicochemical properties effects on cholesterol metabolism. Nutr. Res. 20: 585-598.
Jing, X., F. Yang, C. Shao, K. Wei, M. Xie, H. Shen and Y. Shu. 2019. Role of hypoxia in cancer therapy by ‎regulating the tumor microenvironment. Mol. Cancer. 18:157.
Kim, J. B., A. M. Hudson, K. Huang, A. Bannistes, T. J. Jin, G. H. N. Choi, Y. K.Towers and R. E. Hong. 1997. Biological activity of seaweed extracts from British, Colombia, Canada and Korea. I. Antiviral activity. Can. J. Bot. Rev. 75: 1656 -1660.
Kuda, T., M. Tsunekawa, T. Hishi and Y. Araki. 2005. Antioxidant properties of dried kayamo-nori, a brown alga Scytosiphon lomentaria (Scytosiphonales, Phaeophyceae). Food Chem. 89: 617-622.
Kumar, V. and S. M. Jain. 2014. Plants and algae species: Promising renewable energy production source. Emir. J. Food Agric. 26 (8): 679-692.
Li, J., H. Huang, L. Sun, M. Yang, C. Pan, W. Chen, D. Wu, Z. Lin, C. Zeng, Y. Yao, P. Zhang and E. Song. 2009. MiR-21 indicates poor ‎prognosis in tongue squamous cell carcinomas as an apoptosis inhibitor. Clin. Canc. ‎Res. 15: 3998-4008.
Livak, K. J. and T. D. Schmittgen. 2001. Analysis of relative gene expression data using ‎real-time ‎quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 25: 402-408.
Mayer, A. M. S., A. D. Rodriguez, R. G. S. Berlinck and M. T. Hamann. 2007. Marine pharmacology in ‎‎2003-4: Marine compounds with anthelminthic, antibacterial, anticoagulant, antifungal, ‎antiinflammatory, antimalarial, antiplatelet, antiprotozoal, antituberculosis, and antiviral ‎activities; affecting the cardiovascular, immune and nervous systems, and other miscellaneous ‎mechanisms of action. Comp. Biochem. Physiol. C Toxicol. Pharmacol. 145: 553–581‎‏.‏
McKeown, S. R. 2014. Defining normoxia, physoxia and hypoxia in tumours—implications for treatment ‎response. Br. J. Radiol. 87: 20130676.‎
Mylonis, I., G. Simos and E. Paraskeva. 2019. Hypoxia-Inducible Factors and the Regulation of Lipid ‎Metabolism. Cells. 2019: 8.‎
Nagai, T. and T. Yukimoto. 2003. Preparation functional properties of beverages made from sea algae. Food Chem. 81: 327-332.
Nagaraju, G. P., P. V. Bramhachari, G. Raghu and B. F. El-Rayes. 2015. Hypoxia inducible factor-1: its role in colorectal carcinogenesis and metastasis. Cancer Lett. 366:11-18.
Puisségur, M. P., N. M. Mazure, T. Bertero, L. Pradelli, S. Grosso, K. Robbe-Sermesant, T. Maurin, K. Lebrigand, B. Cardinaud, V. Hofman, S. Fourre, V. Magnone, J. E. Ricci., J. Pouysségur, P. Gounon, P. Hofman, P. Barbry and B. Mari. 2011. miR-‎‎210 is overexpressed in late stages of lung cancer and mediates mitochondrial ‎alterations associated with modulation of HIF-1 activity. Cell Death Diff. 18: 465-478. ‎
Raafat, E. M., A. M. Gamal-Eldeen, E. A. El-Hussieny, E. F. Ahmed and A. A. Eissa. 2014. Polysaccharide extracts of the brown alga Sargassum asperifolium possess in vitro cancer chemopreventive properties. Nat. Prod. Res. 28: 2304–2311.
Roma-Rodrigues, C., R. Mendes, P. V. Baptista and A. R. Fernandes. 2019. Targeting tumor microenvironment ‎for Cancer therapy. Int. J. Mol. Sci. 2019: 20.‎
Santoyo-Ramos, P., M. Likhatcheva, E. A. García-Zepeda, M. C. Castaneda-Patlán and M. Robles-Flores. 2014. Hypoxia-inducible factors modulate the stemness and malignancy of colon cancer cells by playing opposite roles in canonical Wnt signaling. PLoS One. 9: e112580.
‎Selcuklu, S. D., M. T. Donoghue and C. Spillane, 2009. miR-21 as a key regulator of ‎oncogenic processes. Biochem. Soc. Trans. 37: 918-925. ‎
Semenza, G. L. 2003. Targeting HIF-1 for cancer therapy. Nat. Rev. Cancer 3: 721-732‎.
Shao, C., F. Yang, S. Miao, W. Liu, C. Wang, Y. Shu and H. Shen. 2018. Role of hypoxia induced exosomes in ‎tumor biology. Mol. Cancer. 17: 120.‎
Suryaningrum L. H., and R. Samsudin. 2020. Nutrient digestibility of green seaweed Ulva meal and the influence on growth performance of Nile tilapia (Oreochromis niloticus). Emir. J. Food Agric. 32(7): 488-494
Vadde, R., S. Vemula, R. Jinka, N. Merchant, P. V. Bramhachari and G. P. Nagaraju. 2017. Role of hypoxia-inducible factors (HIF) in the maintenance of stemness and malignancy of colorectal cancer. Crit. Rev. Oncol. Hematol. 113: 22-27.
Van Uden, P., N. S. Kenneth, R. Webster, H. A. Muller, S. Mudie and S. Rocha. 2011. Evolutionary conserved ‎regulation of HIF-1beta by NF-kappa b. PLoS Genet. 7: e1001285.
Varol, N., E. Konac, O. S. Gurocak and S. Sozen. 2011. The realm of microRNAs in ‎cancers. Mol. Biol. Rep. 38: 1079-1089.
Vaupel, P. and A. Mayer. 2007. Hypoxia in cancer: significance and impact on clinical outcome. Cancer Metastasis Rev. 26: 225-239.
Wen, X. Q., X. L. Qian, H. K. Sun, L. L. Zheng, W. Q. Zhu, T. Y. Li and J. P. Hu. 2020. MicroRNAs: Multifaceted Regulators of Colorectal Cancer Metastasis and Clinical Applications. OncoTargets therap. 13: 10851-10866.
Wilson, W. R. and M. P. Hay. 2011. Targeting hypoxia in cancer therapy. Nat. Rev. Cancer. 11: 393-410.
‎‎‎Yu, T., B. Tang and X. Sun. 2017. Development of Inhibitors Targeting Hypoxia-Inducible ‎Factor 1 and 2 for Cancer Therapy. Yonsei Med. J. 58: 489-496. ‎
Zagorska, A. and J. Dulak. 2004. HIF-1: the knowns and unknowns of hypoxia sensing. Acta Biochim. Pol. 51: 563-585. ‎
Zhuang, C., H. Itoh, T. Mizuno and H. Ito. 1995. Antitumor active fucoidan from the brown seaweed, ‎umitoranoo (Sargassum thunbergii). Biosci. Biotechnol. Biochem. 59: 563-567.



How to Cite

Eldeen, A. M. G.-., B. M. Raafat, S. M. ‎El-. Daly, C. A. Fahmy, M. M. Almehmadi, and F. Althobaiti. “Inhibitory Effect of Sargassum Latifolium Extract on Hypoxia Pathway in Colon Cancer Cells”. Emirates Journal of Food and Agriculture, vol. 33, no. 7, Aug. 2021, pp. 600-6, doi:10.9755/ejfa.2021.v33.i7.2727.



Research Article